The objectives of this program are directed toward a) the investigation and delineation of the sensitivity and responses to ionizing radiation, hyperthermia, and selected therapeutic chemicals of proliferating endothelial cells in vessels induced by angiogenesis factors from tumor tissue, b) the investigation of the consequences of these responses on the integrity of the microvasculature with regard to changes in the form, number, and patency of vessels, and c) development of a base of knowledge, concerning endothelial and vascular responses to therapeutic agents, which is essential for the investigation of vascular mechanisms involved in the response of tumor parenchymal tissue to therapeutic treatment. An actively proliferating vascular tissue, analogous to that in tumors, induced in otherwise normal tissue, will be used to study the responses of endothelial cells and vessels following exposure to ionizing radiation, to hyperthermia, and to selected chemotherapeutic agents given separately in single exposures or doses. Quantitation of the responses will be made using autoradiographic and quantitative histologic techniques.